CN1181376A - Production of benzophenone derivatives - Google Patents
Production of benzophenone derivatives Download PDFInfo
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- CN1181376A CN1181376A CN 97120201 CN97120201A CN1181376A CN 1181376 A CN1181376 A CN 1181376A CN 97120201 CN97120201 CN 97120201 CN 97120201 A CN97120201 A CN 97120201A CN 1181376 A CN1181376 A CN 1181376A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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Abstract
A method for producing a compound of the formula: wherein R is an acyl group or a silyl group, the rings A and B respectively may have one to four substituent(s), or a salt thereof, which comprists reacting a compound of the formula: wherein R has the same meaning as defined above, the ring A may have one to four substituents at the position(s) other than 2-position, or a salt thereof, with a compound of the formula: wherein Y is a hydroxyl group or a halogen atom, the ring B may have one to four substituent(s), or its salt, in the presence of a catalyst other than polyphosphonic acid. The method produces aminobenzophenone derivative of the formula (I) in a high purity, a high yield, with a conventional and commercially advantageous procedure.
Description
The present invention relates to produce the method for benzophenone derivates, benzophenone derivates is to produce as antiphlogiston the important intermediate of the quinoline of medicines such as antirheumatic or quinazoline.
EP608870A (JPA7-118266) discloses quinoline or the quinazoline derivant as antiphlogiston (the particularly medicine of treatment of arthritis) or antirheumatic, and disclosing has an amino substituent benzophenone derivates as the raw material of producing above-mentioned quinoline or quinazoline derivant in the 2-position.
JPA60-87248 discloses and has comprised that the aniline compound that makes Benzoyl chloride and para-orientation reacts the method for producing 2-aminobenzophenone compound in the presence of Vanadium Pentoxide in FLAKES, and the aniline that makes phenylformic acid and para-orientation reacts the method for producing the 2-aminobenzophenone in the presence of phosphorus pentachloride and/or phosphorus oxychloride, but the document does not have the production technology of public use friedel-crafts catalysts such as metal halide catalyst, and the raw material that uses in this production method is limited in the aniline of halogen atom or low alkyl group para-orientation.
JPA6-172252 discloses the method for producing benzophenone cpd, it comprises makes unsubstituted or has 1-3 to be selected from hydroxyl, alkoxyl group, alkyl, the benzene derivative of aryl and halogenic substituent is selected from hydroxyl with 1-3 is arranged, alkoxyl group, alkyl, the substituent aromatic carboxylic acids of aryl and halogen is at friedel-crafts catalysts and C
1-8Alcohol or the existence of water reaction down.
JPA4-21651,5-70397 and 6-172253 disclose the method for producing the polyhydroxybenzophenone compound, phenol and aromatic carboxylic acid are reacted in the presence of friedel-crafts catalysts, the reaction solvent that uses is selected from alkylsulphonic acid respectively, tetramethylene sulfone and alkyl or aryl phosphine oxide (or sulfide).
Benzophenone derivates not only is to produce various medicines such as antiphlogiston as mentioned above, the synthetic intermediate of antirheumatic etc., and be agricultural chemicals, dyestuff, polymkeric substance, uv-absorbing agent, synthetic resin stable agent, therefore the intermediate of photoetching sensitizing agent etc. need set up a kind of business method of producing them.
The method that the purpose of this invention is to provide a kind of commercially beneficial production benzophenone derivates.
Situation according to above-mentioned prior art, the present inventor has carried out deep research, discovery can prepare the benzophenone derivates that substituted-amino is arranged in the 2-position by the amide compound that makes the N-phenyl and replace and phenylformic acid or the reaction of benzoyl halogen, productive rate is good, the purity height, and do not form by product.According to above-mentioned discovery the present invention has been proposed.
The present invention is:
(1) method of production following formula (I) compound or its salt:
Wherein R is acyl group or silyl, and ring A and B can have 1-4 substituting group respectively, and it comprises makes formula (II) compound or its salt:
Wherein the definition of R is the same, and ring A can have 1-4 substituting group on other positions beyond the 2-position, and the reaction of formula (III) compound or its salt:
Wherein Y is hydroxyl or halogen, and ring B can have 1-4 substituting group, is reflected under the catalyzer existence except Tripyrophosphoric acid to carry out;
Method described in (2) (1) bars, wherein the ring A of compound (I) is at the 5-substd;
Method described in (3) (1) bars, wherein the ring A of compound (I) is at 4-position and 5-substd;
Method described in (4) (1) bars, catalyzer wherein is a friedel-crafts catalysts;
Method described in (5) (4) bars, friedel-crafts catalysts wherein is a metal halide;
Method described in (6) (5) bars, metal halide wherein is a tin halides;
Method described in (7) (4) bars, wherein phosphorous oxychloride or phosphorus trichloride are also as catalyzer;
Method described in (8) (1) bars, the substituting group that wherein encircles on A and/or the ring B is respectively the hydroxyl that replaces, and replaces or unsubstituted alkyl, replaces or unsubstituted acyl, perhaps halogen atom;
Method described in (9) (1) bars, at least one substituting group that wherein encircles on A or the ring B is C
1-6Alkoxyl group;
Method described in (10) (1) bars, the substituting group that wherein encircles on A and the ring B is respectively two C
1-6Alkoxyl group;
Method described in (11) (1) bars, wherein R is formula-CO-R
1Group, R wherein
1Be C unsubstituted or that replace
1-6Alkyl;
Method described in (12) (1) bars, wherein R is an ethanoyl.
It below is the preferred embodiment of definition and each definition of each term relevant that use in the specification sheets with the present invention.
As the above-mentioned ring A that points out and ring B can have respectively 1-4 substituting group (but for ring A, suppose the 2-position promptly any one in two ortho positions be unsubstituted), encircling B can have the individual inactive substituting group of 1-4.
Substituting group on ring A and/or the ring B comes down to inactive, comprises halogen, nitro, the alkyl that can replace, the hydroxyl that can replace, the sulfydryl that can replace, the amino that can replace, the acyl group that can replace, the carboxyl of esterification, formamyl, N-list-C
1-4Alkyl-carbamoyl, N, N-two-C
1-4Alkyl-carbamoyl, ring aminocarboxyl, C
1-6Alkanoyl amino, formamyl amino, N-C
1-4Alkyl-carbamoyl amino, N, N-two-C
1-4Alkyl-carbamoyl amino, C
1-10Alkyl sulphinyl amino, C
1-10Alkyl sulfonyl-amino, 3-6 unit heterocyclic amino group, cyano group, alkylsulfonyl, sulfinyl, phosphono, amino-sulfonyl, the especially preferred hydroxyl that can replace, the alkyl that can replace, acyl group that can replace and halogen.
Comprise fluorine as substituent halogen on ring A or B, chlorine, bromine and iodine, preferred fluorine and chlorine.
As the substituent alkyl on ring A or the B, can be substituted, can be the straight chain of any 1-10 of having carbon atom, side chain (C
3-10), ring-type (C
3-10) alkyl, methyl for example, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, isopentyl, neo-pentyl, hexyl, heptyl, octyl group, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and suberyl; As the C that replaces
1-10Alkyl can be by 1-3 halogen atom (as fluorine, chlorine, bromine and iodine), amino, and hydroxyl, amide group, cyano group, nitro is by C
1-3The carboxyl substituted of alkyl (as methyl, ethyl, propyl group, sec.-propyl) esterification, the preferred C that replaces
1-10Alkyl is halo C
1-6Alkyl (for example chloromethyl, dichloromethyl, trifluoromethyl, trifluoroethyl).
As the substituent hydroxyl on ring A or the B, can be substituted, for example be hydroxyl or suitable substituting group is arranged; particularly contain substituent hydroxyl as hydroxyl protecting group, as alkoxyl group, alkenyloxy; alkynyloxy group and acyloxy, described alkoxyl group are the alkoxyl group that preferably has 1-10 carbon atom (methoxyl group for example, oxyethyl groups; propoxy-, isopropoxy, butoxy; isobutoxy; sec-butoxy, tert.-butoxy, pentyloxy; isopentyloxy; neopentyl oxygen, hexyloxy, heptan the oxygen base; the ninth of the ten Heavenly Stems oxygen base; cyclobutoxy group, cyclopentyloxy, cyclohexyloxy).Described alkenyloxy for example is the alkenyloxy that 2-10 carbon atom arranged, as allyloxy, and butenyloxy, 2-amylene oxygen base, 3-hexene oxygen base, 2-cyclopentenes methoxyl group and 2-tetrahydrobenzene methoxyl group.C
2-10Alkynyloxy group for example is the second alkynyloxy group, 2-third alkynyloxy group.Described acyloxy preferably has the alkanoyloxy (acetoxyl group for example, propionyloxy, positive butyryl acyloxy, isobutyl acyloxy) of 2-4 carbon atom, can substituted hydroxyl be C preferably
1-10Alkoxyl group, more preferably C
1-6Alkoxyl group, as methoxyl group, oxyethyl group, propoxy-and isopropoxy.
As the substituent sulfydryl on ring A or the B, it can be substituted, for example be sulfydryl or suitable substituting group is arranged, and in particular as the substituent sulfydryl of the protecting group of sulfydryl, as alkylthio, alkenyl thio, alkynes sulfenyl and acyl sulfenyl.Described alkylthio preferably has alkylthio (methylthio group for example, ethylmercapto group, the rosickyite base of 1-10 carbon atom, the iprotiazem base, positive butylthio, isobutyl sulfenyl, secondary butylthio, uncle's butylthio, penta sulfenyl, the isoamyl sulfenyl, new penta sulfenyl, own sulfenyl, heptan sulfenyl, the ninth of the ten Heavenly Stems sulfenyl, the ring butylthio, encircle penta sulfenyl, the hexamethylene sulfenyl).Described alkenyl thio for example is C
2-10Alkenyl thio (for example allyl sulfenyl, butylene sulfenyl, 2-amylene sulfenyl, 3-hexene sulfenyl, 2-cyclopentenes sulfenyl, 2-tetrahydrobenzene sulfenyl).Described alkynes sulfenyl for example is C
2-10Alkynes sulfenyl (for example acetylene sulfenyl, 2-propine sulfenyl).Described acyl mercapto preferably has the alkyl acyl sulfenyl (acetylthio for example, propionyl sulfenyl, positive butyryl sulfenyl, isobutyryl sulfenyl) of 2-4 carbon atom.
As the substituent amino on ring A or the B; it can be substituted; for example be amino and by the alkyl of 1 or 2 1-10 carbon atom, the alkenyl of 2-10 carbon atom, the alkynyl of 2-10 carbon atom; aryl; heterocyclic radical and amino (methylamino-for example, dimethylamino, the ethylamino of the acyl substituted of 1-10 carbon atom are arranged; diethylin; dibutylamino, two allyl amino, hexamethylene amino; phenylamino; N-methyl-N phenyl-amino, acetylamino, propionyl amino; benzoyl-amido, nicotinoyl amino etc.).
Acyl group for example is a formyl radical and with the alkyl of 1-10 carbon atom, and the alkenyl of 2-10 carbon atom, the alkynyl of 2-10 carbon atom, aryl are connected the group that formyl radical obtains (ethanoyl for example with carbonyl; propionyl, butyryl radicals, isobutyryl, pentanoyl; isovaleryl, valeryl, caproyl, oenanthyl; capryloyl, ring butyryl radicals, ring pentanoyl; the hexamethylene acyl group, ring oenanthyl, crotonoyl; 2-tetrahydrobenzene acyl group, benzoyl, nicotinoyl).Substituting group on the acyl group can be identical with the substituting group on the alkyl.
As the substituent carboxyl on ring A or the B, it can be esterified, for example is carbalkoxy, alkenyl oxygen carbonyl, and alkynes oxygen carbonyl and acyl-oxygen carbonyl, these groups for example are the group of following formula :-COOR
3, R wherein
3Be C
1-6Alkyl, the alkyl in the above-mentioned carbalkoxy etc. for example is the alkyl that 1-6 carbon atom arranged, as methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl.
As the substituent N-list-C on ring A or the B
1-4Alkyl-carbamoyl includes but not limited to N-methylamino formyl radical, N-ethylamino formyl radical, N-propyl group formamyl, N-sec.-propyl formamyl and N-butyl formamyl.
As the substituent N on ring A or the B, N-two-C
1-4Alkyl-carbamoyl includes but not limited to N, N-formyl-dimethylamino, N, N-diethylamino formyl radical, N, N-dipropyl formamyl, and N, N-dibutylamino formyl radical.
Include but not limited to 1-azacyclopropane base carbonyl, 1-azetidinyl carbonyl, 1-pyrrolidyl carbonyl, 1-pyridyl carbonyl and N methyl piperazine base carbonyl, morpholinyl carbonyl, and thio-morpholinyl carbonyl as the substituent ring aminocarboxyl on ring A or the B.
As the substituent C on ring A or the B
1-6The alkyloyl amide group includes but not limited to formamido group, kharophen, trifluoroacetamido, propionamido, butyrylamino and isobutyryl amino.
As the substituent N-C on ring A or the B
1-4Alkyl-carbamoyl amino includes but not limited to N-methylamino formyl radical amino, N-ethylamino formyl radical amino, N-propyl group formamyl amino, the amino and N-butyl formamyl amino of N-sec.-propyl formamyl.
As the substituent N on ring A or the B, N-two-C
1-4Alkyl-carbamoyl amino includes but not limited to N, N-formyl-dimethylamino amino, N, N-diethylacbamazine acyl amino, N, N-dipropyl formamyl amino and N, N-dibutylamino formyl radical amino.
As the substituent C on ring A or the B
1-10Alkyl sulphinyl includes but not limited to methylsulfinyl, ethyl sulfinyl, propyl group sulfinyl and butyl sulfinyl.C
1-10Alkyl sulphonyl includes but not limited to methyl sulphonyl, ethylsulfonyl, sulfonyl propyl base and butyl alkylsulfonyl.
3-6 unit heterocyclic amino group is selected from oxygen except comprising as the carbon atom of link and the nitrogen-atoms, can also containing, and the 1-3 of sulphur and nitrogen heteroatomic 3-6 unit heterocyclic amino group is (as the ethylenimine base, azetidinyl, pyrrolidyl, pyrrolinyl, pyrryl, imidazolyl, pyrazolyl, imidazolinyl, piperidino-(1-position only), morpholinyl, thio-morpholinyl, dihydropyridine base, pyridyl, the N methyl piperazine base, N-ethyl piperazidine base etc.).
Substituting group on the above-mentioned ring A can be in ring and go up any position in addition, 2-position (being the ortho position), can be in any position for the substituting group on the ring B.Preferred ring A is substituted in the 5-position (the 4-position of formula (II) compound) of formula (I) compound, more preferably encircle A in the 4-position and/or the 5-position be substituted, the ring B preferably in the 3-position and/or the 4-position be substituted, when two or more substituting group, these substituting groups can be identical or different, substituent quantity on each ring is 1-4, preferred 1-2.
When any two substituting groups on ring A or the ring B were adjacent one another are, they can be connected to form formula-(CH
2)
m-or-O-(CH
2)
nThe ring of-O-, wherein m represents the integer of 3-5, and n represents the integer of 1-3, and two carbon atoms of each ring and phenyl ring form 5-7 unit ring system together.
Preferred substituted on ring A and/or the ring B is respectively the hydroxyl that replaces, and replaces or unsubstituted alkyl, replaces or unsubstituted aryl, perhaps halogen atom.
Wherein preferably encircling the substituted situation of A is that (1) wherein encircles A for example alkoxy or hydroxyl replacement; (2) wherein encircle A and replaced (particularly in 4-position and 5-position) by two identical or different alkoxyl groups; (3) wherein encircle A 4, the 5-position is replaced by methylene-dioxy.Particularly preferred situation be ring A in 4-position and 5-position by C
1-6Alkoxyl group, preferably methoxyl group is two replaces.
Wherein preferably encircling the substituted situation of B is that (1) wherein encircles B for example alkoxy or hydroxyl replacement; (2) wherein encircle B and replaced (particularly being replaced by methoxyl group and/or isopropoxy) by two identical or different alkoxyl groups at 3-and 4-position; (3) wherein encircling B is replaced by methylene-dioxy.Particularly preferred situation be ring B in 3-position and 4-position by C
1-6Alkoxyl group, particularly methoxyl group are two to be replaced.
For formula (II) and formula (I), R represents acyl group or silyl, and above-mentioned acyl group is with formula-CO-R
1Expression (R
1Represent unsubstituted or by C
1-5The group that alkyl replaces).R
1C
1-6Alkyl comprises methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, isopentyl, neo-pentyl, tert-pentyl, 1-ethyl propyl etc., preferred especially C
1-5Alkyl, more preferably C
1-3Alkyl such as methyl or ethyl.As the substituting group on the alkyl can be 1-3 halogen atom (for example fluorine, chlorine, bromine, iodine), amino, and hydroxyl, amido, cyano group, nitro is used C
1-3The carboxyl of alkyl (for example methyl, ethyl, propyl group sec.-propyl) esterification.
Above-mentioned silyl includes 2 or 3 and is selected from C
1-6Alkyl (for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, hexyl), C
1-3Alkoxyl group (methoxyl group for example, oxyethyl group) and the silyl of phenyl group, as trimethyl silyl, dimethyl sec.-propyl silyl, the tertiary butyl-dimetylsilyl, di-t-butyl methyl-silicane base, hexyl-dimetylsilyl, triethylsilyl, triisopropyl silyl, the triphenyl silyl, diethyl sec.-propyl silyl, diphenyl methyl silyl, the tertiary butyl-diphenylmethyl silylation, the tertiary butyl-methoxyphenyl silyl etc., preferred especially trimethyl silyl, dimethyl sec.-propyl silyl, t-butyldimethylsilyl, di-t-butyl methyl-silicane base, and hexyl-dimetylsilyl.In formula (II) and the R (I) preferably represent C
1-6Acyl group such as ethanoyl, propionyl, butyryl radicals etc., more preferably R is an ethanoyl.
In formula (III), Y represents hydroxyl or halogen, preferred hydroxyl, and the halogen that Y represents comprises fluorine, chlorine, bromine and iodine, preferred chlorine.
In formula (III) compound, wherein Y is that the compound (being that compound is a carboxylic acid halides) of halogen can pass through known method, for example use mineral acid halogenide (phosphorus pentachloride for example, phosphorus trichloride, phosphorus tribromide, thionyl chloride, thionyl bromide, phosphoryl chloride, oxalyl chloride etc., preferred thionyl chloride or phosphoryl chloride) to handle Y wherein be that the corresponding compounds (being aromatic carboxylic acid) of hydroxyl prepares.
As formula (I), when (II) and/or (III) compound contains basic group such as amino, they can and mineral acid (hydrochloric acid for example, phosphoric acid, Hydrogen bromide, sulfuric acid), organic acid (acetate for example, formic acid, propionic acid, fumaric acid, toxilic acid, succsinic acid, citric acid, oxysuccinic acid, oxalic acid, phenylformic acid, methylsulfonic acid, Phenylsulfonic acid) formation salt.
As formula (I), when (II) and/or (III) compound contained acidic-group such as mercapto groups, they can form salt with mineral alkali such as basic metal or alkaline-earth metal (for example sodium, potassium, calcium, magnesium) or ammonia, perhaps with organic bases as three-C
1-3Alkylamine (for example triethylamine) forms salt.
In various formulas (II) compound, preferred compound is:
N-(3, the 4-dimethoxy phenyl) ethanamide,
N-(3-hydroxyl-4-methoxyphenyl) ethanamide,
N-(4-hydroxyl-3-methoxyphenyl) ethanamide and
N-(3, the 4-methylene dioxy phenyl group) ethanamide.
N-(3, the 4-dimethoxy phenyl) ethanamide most preferably.
In various formulas (III) compound, particularly preferred compound is:
3, the 4-dimethoxybenzoic acid,
3-hydroxyl-4-methoxybenzoic acid,
Vanillic acid,
Piperonylic acid.
Most preferably 3, the 4-dimethoxybenzoic acid.
In various formulas (I) compound, particularly preferred compound is:
2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', 5-tetramethoxy benzophenone,
2-acetylaminohydroxyphenylarsonic acid 3 '-isopropoxy-4,4 ', 5-trimethoxy benzophenone,
2-acetylaminohydroxyphenylarsonic acid 4-hydroxyl-3 ', 4 ', 5-trimethoxy benzophenone,
2-acetylaminohydroxyphenylarsonic acid 3 '-hydroxyl-4,4 ', 5-trimethoxy benzophenone and
2-acetylaminohydroxyphenylarsonic acid 5-hydroxyl-3 ', 4,4 '-the trimethoxy benzophenone.
Most preferably 2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', 5-tetramethoxy benzophenone.
The organic solvent that uses in the reaction of the inventive method can reasonably be selected from for formula (II) compound or its salt, formula (III) compound or its salt, and the aminobenzophenone compound or its salt of formula (I) is an inert, does not influence the solvent of reaction, preferred halohydrocarbon, as methylene dichloride, 1, the 2-ethylene dichloride, 1, propylidene chloride 1,1,2-propylene dichloride, 1,3-propylene dichloride, 2,2-propylene dichloride, 1,4-dichlorobutane, 2,3-dichlorobutane, 1-chlorobutane, Sec-Butyl Chloride, chloroform etc.The ratio of organic solvent is at least about 5 times of weight equivalents of formula (II) compound or its salt usually, preferably about 10-15 times of weight equivalent.
Formula (II) compound or its salt that uses as raw material in the inventive method and the relative consumption of formula (III) compound or its salt normally every mole of formula (II) compound or its salt use about 1-3 mole, formula (III) compound or its salt of preferably approximately 1.1-1.5 mole.
This is reflected at catalyzer except Tripyrophosphoric acid and carries out under existing.
Reaction of the present invention is preferably carried out in the presence of friedel-crafts catalysts, operable friedel-crafts catalysts comprises the metal halide catalyst (halogenide of aluminium for example, the halogenide of gallium, the halogenide of zirconium, the halogenide of antimony, the halogenide of molybdenum, the halogenide of zinc, the halogenide of tin, the halogenide of iron, the halogenide of boron, the halogenide of titanium, the halogenide of bismuth etc.), the halogenide such as the tin chloride (II) of preferred especially tin, tin chloride (IV), Tin tetrabromide (II), Tin tetrabromide (IV).The ratio of the friedel-crafts catalysts that uses is that every mole of formula (II) compound or its salt is about the 1-3 mole, preferred 1.1-1.8 mole.
In addition, the above-mentioned friedel-crafts catalysts of reaction preferred combination of the inventive method uses Phosphorates phosphorus Halides (for example phosphorous oxychloride, phosphorus trichloride) to finish together, as specific examples, tin chloride and phosphorous oxychloride is used in combination.The ratio of used Phosphorates phosphorus Halides is that every mole of formula (II) compound or its salt approximately uses the 3-12 mole, preferably about 5-8.5 mole.
The temperature of finishing the present invention's reaction is approximately 0 ℃-83 ℃, preferred about 40 ℃-50 ℃.When temperature of reaction was low, speed of response was slack-off.
About 5-30 of the reaction times of the inventive method hour, preferably approximately 12-16 hour, the reaction times should be according to the type and the quantity adjustment of temperature of reaction and catalyzer.
The aminobenzophenone derivative (I) that the inventive method is produced or its salt can be separated according to known separation-method of purification own, as concentrating, concentrating under reduced pressure, solvent extraction and crystalline method, if need, compound can also be further purified according to known purification techniques itself, for example recrystallization.
By known technology such as solvent extraction; concentrate; concentrating under reduced pressure is finished formula (I) compound that postprecipitation goes out in reaction can carry out next step deacylated tRNA radical reaction and other reactions in same reactor, promptly do not need to separate in advance and/or change into the salt (for example hydrochloride) of compound (I).According to EP608870A (JPA7-118266), the international open described method of WO96/00223 (JPA8-67679) of PCT changes following compound, for example, product compound can be derived for multiple pharmaceutically available the finished product compound, as anti-inflammatory agent or rheumatism.Specifically, except other many methods, the method in the following reference example or other similar approach can be used in purpose of the present invention.
Method of the present invention can be with high purity, and high yield is produced aminobenzophenone, and is a kind of commercially beneficial easily method.
The present invention can illustrate in greater detail with following operation embodiment, but is not limited to the explanation of embodiment, in the following embodiments, unless otherwise indicated beyond, percentage ratio " % " is meant weight percentage.
Reference example 1
The preparation of N-(3, the 4-dimethoxy phenyl) ethanamide:
3,4-dimethoxyaniline (153.2g, 1mol) be suspended in the water (350ml), suspension is heated to 80 ℃ ± 5 ℃, under same temperature, stirs the mixture, drip 3, the aqueous sodium hydroxide solution (52.0g/300ml) and 3 of 4-dimethoxyaniline suspension vol 1/5, the diacetyl oxide of 4-dimethoxyaniline suspension vol 1/5 (132.7g, 1.3mol), in 80 ℃ ± 5 ℃ 1/5 aqueous sodium hydroxide solution and the diacetyl oxides that add residual volume in the gained mixture.After being added dropwise to complete, the gained mixture leaves standstill and is cooled to room temperature in 80 ℃ ± 5 ℃ reactions 20 minutes, and mixture further is cooled to below 5 ℃, keep this temperature to finish reaction in 1 hour, filter the crystallization that collecting precipitation goes out with glass funnel, water (306ml) washed twice, the wet crystallization that settles out is in about 45 ℃ of drying under reduced pressure, obtain N-(3, the 4-dimethoxy phenyl) ethanamide, output: 183.43g (93%), purity: 99%.
Reference example 2
3, the preparation of 4-dimethoxy-benzoyl chloride:
Toward 3, the 4-dimethoxybenzoic acid (2.73g, add in 15mmol) thionyl chloride (22.34g, 187.8mmol), the heated and stirred mixture also refluxed 1 hour, and after reaction was finished, reduction vaporization fell excessive thionyl chloride, obtain 3 quantitatively, the 4-dimethoxy-benzoyl chloride is the yellow-white crystallization.
Embodiment 1
2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', the preparation of 5-tetramethoxy benzophenone:
N-(3, the 4-dimethoxy phenyl) ethanamide (9.76g, 50mmol) with 3,4-dimethoxybenzoic acid (13.66g, 75mmol) be suspended in the methylene dichloride (100ml), (65.17g 425mmol), drips tin tetrachloride (23.45g down in being lower than 35 ℃ subsequently to drip phosphorous oxychloride in the gained mixture, 90mmol), heated and stirred gained mixture also refluxed 18 hours, added methylene dichloride (50ml) after reaction is finished in the gained reaction mixture, and the gained mixture is cooled to about 10 ℃, drip water (250ml) subsequently gradually, holding temperature is in about below 35 ℃,, stirring at room gained mixture 10 minutes, left standstill 10 minutes, incline and strain separation, isolated dichloromethane layer is with 10% sodium hydroxide (100ml) solution washing, removes residual 3, the 4-dimethoxybenzoic acid, the gained dichloromethane layer is used pure water (100ml) washing again, and the atmospheric evaporation methylene dichloride obtains residue (27.5g).Add methyl alcohol (100ml) in residue, component distillation steams residual methylene dichloride, and re-treatment once, add methyl alcohol (100ml) in the spissated residue of gained, the crystallization that is settled out is cooled to 10 ℃, leaves standstill 30 minutes, filter the crystallization of collection gained with glass funnel, with methyl alcohol (30ml) drip washing twice, the wet crystallization of gained is in about 40 ℃ of drying under reduced pressure, obtain 2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', 5-tetramethoxy benzophenone, output: 16.4g (88.5%), purity: 96.8%.
1H-NMR(DMSO-d
6，90MHz)δ：2.21(3H，s，-NHCOCH
3)，
3.76(3H，s，OMe)，3.93(3H，s，OMe)，3.98(3H，s，
OMe)，4.00(3H，s，OMe)，6.87-7.35(4H，m，arom)，
8.39(1H，s，arom)，11.05(1H，brs，-NHCOCH
3).
Ultimate analysis: (C
19H
21O
6N)
Calculated value (%): C:63.50, H:5.89, O:26.71, N:390
Measured value (%): C:63.32, H:5.84, O:26.99, N:3.85
Fusing point: 153-156 ℃
Embodiment 2
2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', the preparation of 5-tetramethoxy benzophenone:
N-(3, the 4-dimethoxy phenyl) ethanamide (1.95g, 10mmol) with 3,4-dimethoxy-benzoyl chloride (2.61g, 13mmol) be suspended in the methylene dichloride (20ml), drip phosphorous oxychloride (4.60g subsequently, 30mmol), drip tin tetrachloride (4.69g down in being lower than 35 ℃ subsequently, 18mmol), heated and stirred gained mixture also refluxed 10 hours, after finishing, reaction in the gained reaction mixture, adds methylene dichloride (10ml), the gained mixture is cooled to about 10 ℃, drip water (50ml) subsequently gradually, added back stirring at room mixture 10 minutes, left standstill 10 minutes, and inclined and strain separation, the gained dichloromethane layer is with 10% sodium hydroxide (20ml) solution washing, remove residual 3, the 4-dimethoxybenzoic acid is used pure water (20ml) washing again, and reduction vaporization is removed methylene dichloride, get residue (3.85g), add methyl alcohol (20mL) in the gained residue, the decompression component distillation repeats this operation once to remove remaining methylene dichloride, in the spissated residue of gained, add methyl alcohol (20ml), the crystallization that is settled out is cooled to 10 ℃, leaves standstill 1 hour, and the wet crystallization of gained is in about 40 ℃ of drying under reduced pressure, obtain 2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', 5-tetramethoxy benzophenone, output: 2.87g (80.1%), purity: 98.4%.
Reference example 3
2-amino-3 ', 4,4 ', the preparation of 5-tetramethoxy benzophenone hydrochloride:
N-(3, the 4-dimethoxy phenyl) ethanamide (19.52g, 100mmol) with 3,4-dimethoxybenzoic acid (27.32g, 150mmol) be suspended in the methylene dichloride (200ml), drip phosphorous oxychloride (130.34g down in being lower than 35 ℃ subsequently, 850mmol), in be lower than 35 ℃ drip in the mixture down tin tetrachloride (46.9g, 180mmol), the heated and stirred reaction mixture also refluxed 20 hours, in the gained mixture, add methylene dichloride (100ml) after reaction is finished, be cooled to below 10 ℃, drip water (500ml) subsequently gradually, careful initial stage heating, holding temperature are in about below 35 ℃.
Stirring at room gained mixture 10 minutes, left standstill 10 minutes, and inclined and strain separation, the gained dichloromethane layer is with 10% sodium hydroxide (200ml) solution washing, remove residual 3,4-dimethoxybenzoic acid, dichloromethane layer are used pure water (200ml) washing, air distillation methylene dichloride again, obtain containing 2-kharophen 3 ', 4,4 ', the residue (78.4g) of 5-tetramethoxy benzophenone.
In the gained residue, add concentrated hydrochloric acid (115.5ml) and isopropylcarbinol (387ml), subsequently in stirring down in 75 ℃ ± 5 ℃ backflow mixtures 2 hours, after reaction is finished, the gained reaction mixture is cooled to 10 ℃ ± 5 ℃, left standstill 2 hours, filter the crystallization that collection is settled out with glass funnel, wash with isopropylcarbinol (116ml), the wet crystallization of gained is in about 45 ℃ of drying under reduced pressure, obtain 2-amino-3 ', 4,4 ', 5-tetramethoxy benzophenone hydrochloride, output: 32.2g (89.8%), purity 98.6%.
1H-NMR(DMSO-d
6，90MHz)δ：3.64(3H，s，OMe)，3.81
(3H，s，OMe)，3.83(3H，s，OMe)，3.86(3H，s，OMe)，
6.92-7.32 (5H, m, arom), 7.72 (3H, brs ,-NH
2And HCl).
Ultimate analysis: (C
17N
20O
5NCl)
Calculated value (%): C:57.71, H:5.70, O:22.61, N:3.96
Cl：10.02
Measured value (%): C:57.43, H:5.71, O:22.80, N:4.36,
Cl：9.70
Fusing point: 198-201 ℃
Reference example 4
2-amino-3 ', 4,4 ', the preparation of 5-tetramethoxy benzophenone hydrochloride:
N-(3, the 4-dimethoxy phenyl) ethanamide (9.76g, 50mmol) with 3,4-dimethoxybenzoic acid (10.02g, 55mmol) be suspended in the methylene dichloride (100ml), drip phosphorous oxychloride (38.33g down in being lower than 35 ℃ subsequently, 250mmol), in be lower than 40 ℃ drip in the mixture down tin tetrachloride (23.45g, 90mmol), the heated and stirred reaction mixture also refluxed 24 hours, in the gained mixture, add methylene dichloride (50ml) after reaction is finished, be cooled to below 10 ℃, drip water (250ml) subsequently gradually, careful attention initial stage heating, holding temperature are in about below 35 ℃.
Stirring at room gained mixture 10 minutes, left standstill 10 minutes, and inclined and strain separation, the gained dichloromethane layer washs with 3% aqueous sodium hydroxide solution (100ml), remove residual 3,4-dimethoxybenzoic acid, dichloromethane layer are used pure water (100ml) washing again, and methylene dichloride is fallen in air distillation, obtain containing 2-kharophen 3 ', 4,4 ', the residue (41.8g) of 5-tetramethoxy benzophenone.
In the gained residue, add concentrated hydrochloric acid (57.7ml) and isopropylcarbinol (193ml), subsequently in stirring down in 75 ℃ ± 5 ℃ backflow mixtures 2 hours, after reaction is finished, the gained reaction mixture is cooled to 10 ℃ ± 5 ℃, kept same temperature 2 hours, filter the crystallization that collection is settled out with glass funnel, wash with isopropylcarbinol (58ml), the wet crystallization of gained is in about 45 ℃ of drying under reduced pressure, obtain 2-amino-3 ', 4,4 ', 5-tetramethoxy benzophenone hydrochloride, output: 16.1g (89.2%), purity: 98.0%.
1H-NMR(DMSO-d
6，90MHz)δ：3.64(3H，s，OMe)，3.81
(3H，s，OMe)，3.83(3H，s，OMe)，3.86(3H，s，OMe)，
6.92-7.32 (5H, m, arom), 7.72 (3H, brs ,-NH
2And HCl).
Ultimate analysis: (C
17N
20O
5NCl)
Calculated value (%): C:57.71, H:5.70, O:22.61, N:3.96
Cl：10.02
Measured value (%): C:57.43, H:5.71, O:22.80, N:4.36,
Cl：9.70
Fusing point: 198-201 ℃
Reference example 5
The preparation of N-(3, the 4-dimethoxy phenyl) ethanamide:
3,4-dimethoxyaniline (100g) is suspended in the water (800ml), in the diacetyl oxide (86.6g) that adds aqueous sodium hydroxide solution (34.0g/200ml) and 1/5 volume below 65 ℃ in the suspension, in 55-60 ℃ of stirred reaction mixture 20 minutes, reaction mixture is cooled to about 5 ℃, stirred 1 hour, and filtered the crystallization that collecting precipitation goes out, drying under reduced pressure, obtain N-(3, the 4-dimethoxy phenyl) ethanamide is the burgundy crystallization, output: 119g (93.2%).
The sample re-crystallizing in ethyl acetate, so as with IR and
1H-NMR measures.
IR(cm
-1，KBr)：3276，1653，1606，1575，1520，1462
1H-NMR(CDCl
3，300MHz)δ：2.15(3H，s)，3.84(6H，s)，
6.78(1H，d，J＝8.6Hz)，6.88(1H，dd，J＝8.6，2.4Hz)，7.3?0
(1H，d，J＝2.4Hz)，7.55(1H，brs).
Reference example 6
2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', the preparation of 5-tetramethoxy benzophenone:
With N-(3, the 4-dimethoxy phenyl) ethanamide (114g), 3, the mixture of 4-dimethoxybenzoic acid (117g) and Tripyrophosphoric acid (1203g) stirred 3 hours in 95-110 ℃, in reaction mixture, add cold water (3L), with ethyl acetate (3L) extraction, extraction liquid washes with water then with 2N aqueous sodium hydroxide solution (3L) washing, behind the concentrating under reduced pressure, in residue, add normal hexane (1.2L), mixture was stirred 30 minutes the crystallization that collecting precipitation goes out, drying under reduced pressure obtain 2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', 5-tetramethoxy benzophenone, be yellow crystal, output: 129g (61.3%).
The sample re-crystallizing in ethyl acetate, with measure IR and
1H-NMR.
IR(cm
-1，KBr)：2947，1695，1678，1616，1595
1H-NMR(CDCl
3，300MHz)δ：2.22(3H，s)，3.76(3H，s)，
3.94(3H，s)，3.98(3H，s)，4.00(3H，s)，6.93(1H，d，J＝7.7Hz)，
7.09(1H，s)，7.28(1H，dd，J＝7.7，1.9Hz)，7.32(1H，s)，8.38
(1H，s)，11.0(1H，brs).
Reference example 7
2-amino-3 ', 4,4 ', the preparation of 5-tetramethoxy benzophenone hydrochloride:
With concentrated hydrochloric acid (446ml) join 2-acetylaminohydroxyphenylarsonic acid 3 ', 4,4 ', in the solution of 5-tetramethoxy benzophenone (129g) and isopropylcarbinol (1.49L), reflux mixture 2 hours, cooling gained mixture, in stirring 2 hours below 5 ℃, filter the crystallization that collecting precipitation goes out, drying under reduced pressure obtain 2-amino-3 ', 4,4 ', 5-tetramethoxy benzophenone hydrochloride is faint yellow crystallization, output: 117g (92.3%).
Sample with ethyl alcohol recrystallization after, measure IR and
1H-NMR.
IR(cm
-1，KBr)：3618，2839，2567，1657，1628，1583
1H-NMR(DMSO-d
6，300MHz)δ：3.58(3H，s)，3.80(6H，s)，
3.85(3H，s)，6.61(1H，brs)，6.93(1H，s)，7.06(1H，d，J＝8.6
Hz)，7.20-7.22(2H，m).
Reference example 8
2-chloromethyl-4-(3, the 4-dimethoxy phenyl)-6, the preparation of 7-dimethoxy-quinoline-3-carboxylic acid, ethyl ester:
2-amino-3 ', 4,4 ', 5-tetramethoxy benzophenone hydrochloride (36.0g) and 4-ethyl chloroacetate (21.4g) reflux under stirring in ethanol (350ml) and heated 7 hours, after reaction is finished, in in mixture, dripping triethylamine (10.6g) below 20 ℃, stirred the mixture 1 hour in 5 ℃, filter the crystallization that collecting precipitation goes out, with ethanol (50ml) washed twice, drying under reduced pressure obtains 2-chloromethyl-4-(3, the 4-dimethoxy phenyl)-6,7-dimethoxy-quinoline-3-carboxylic acid, ethyl ester, output: 41.0g (92%).
Reference example 9
4-amino-1-[4-(3, the 4-dimethoxy phenyl)-3-ethoxycarbonyl-6,7-dimethoxy-quinoline-2-ylmethyl]-4H-1,2,4-triazole bromination:
With 2-chloromethyl-4-(3, the 4-dimethoxy phenyl)-6,7-dimethoxy-quinoline-3-carboxylic acid, ethyl ester (22.5g, 50.0mmol, purity: 99.1%), Sodium Bromide (5.81g, 56.5mmol) and 4-amino-1,2, the 4-triazole (5.47g, 65.1mmol) be suspended in dimethyl formamide (DMF) (50ml) in, in 65 ℃ of stirred suspensions 3 hours, in reaction mixture, add ethyl acetate (100ml), filter the crystallization that collecting precipitation goes out, drying, obtain 4-amino-1-[4-(3, the 4-dimethoxy phenyl)-and 3-ethoxycarbonyl-6,7-dimethoxy-quinoline-2-ylmethyl]-4H-1,2,4-triazole bromination, be white crystals, output: 31.1g (90.6%), purity: 83.6%.
Sample silica gel column chromatography (mobile phase: CH as the structure evaluation
2Cl
2: MeOH=5: 1) and recrystallization method (4.8% aqueous ethanol) purify.
IR(cm
-1，KBr)：3196，1706，1518，1472
1H-NMR(DMSO-d
6，90MHz)δ：0.92(3H，t，J＝6.9Hz，
CO
2CH
2CH
3)，3.72(3H，s，OMe)，3.77(3H，s，OMe)，3.86(3
H，s，OMe)，3.96(3H，s，OMe)，3.72-4.09(2H，m，CO
2CH
2)，
5.94(2H，s，CH
2N)，6.93-7.31(7H，m)，9.28(1H，s，CH＝N)，
10.41(1H，s，CH＝N).
Ultimate analysis: (C
25H
28N
5O
5Br (0.73H
2O))
Calculated value (%): C:51.10, H:5.05, N:11.92, Br:13.60
Measured value (%): C:51.10, H:4.91, N:11.88, Br:13.55
Fusing point: 183.8-184.4 ℃
Reference example 10
4-(3, the 4-dimethoxy phenyl)-6, the preparation of 7-dimethoxy-2-(1,2,4-triazol-1-yl methyl) quinoline-3-carboxylic acid ethyl ester:
4-amino-1-[4-(3, the 4-dimethoxy phenyl)-3-ethoxycarbonyl-6,7-dimethoxy-quinoline-2-ylmethyl]-4H-1,2,4-triazole bromination (10.31g, 15.0mmol, purity: 83.6%) be suspended in the water (37.5ml), add concentrated hydrochloric acid (3.8ml down in ice bath subsequently, 45mmol) and the sodium nitrite in aqueous solution (4.00ml of 5.6M, 22.5mmol), stirring at room mixture 2 hours, the aqueous sodium hydroxide solution (8.7ml) that adds 5N in the reaction mixture neutralizes, filter the crystallization that collecting precipitation goes out, obtain 4-(3, the 4-dimethoxy phenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-yl methyl) quinoline-3-carboxylic acid ethyl ester is white crystals, output: 6.66g (92.8%).
IR(cm
-1，KBr)：1720，1504，1468，1430
1H-NMR(CDCl
3，90MHz)δ：0.89(3H，t，J＝7.1Hz，
CO
2CH
2CH
3)，3.79(3H，s，OMe)，3.86(3H，s，OMe)，3.96(3
H，s，OMe)，4.04(3H，s，OMe)，3.86-4.13(2H，q，J＝7.1Hz，
CO
2CH
2)，5.72(2H，s，CH
2N)，6.86-6.95(4H，m)，7.41
(1H，s)，7.93(1H，s)，8.23(1H，s).
Fusing point: 175.4-176.0 ℃
Reference example 11
4-(3, the 4-dimethoxy phenyl)-6, the preparation of 7-dimethoxy-2-(1,2,4-triazol-1-yl methyl) quinoline-3-carboxylic acid ethyl ester:
With 4-amino-1-[4-(3, the 4-dimethoxy phenyl)-3-ethoxycarbonyl-6,7-dimethoxy-quinoline-2-ylmethyl]-4H-1,2,4-triazole bromination (503g, 0.709mol, purity: 80.9%) be suspended in the water (5.44L), subsequently in ice bath add down concentrated hydrochloric acid (159g, 1.56mol) and the sodium nitrite in aqueous solution of 0.63M (1.46L, 0.920mol), stirring at room mixture 3 hours, the aqueous sodium hydroxide solution (295ml) that adds 5N in the reaction mixture neutralizes, and filters the crystallization that collecting precipitation goes out, drying, wash with water, obtain 4-(3, the 4-dimethoxy phenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-yl methyl) quinoline-3-carboxylic acid ethyl ester is white crystals, output: 329g (97.0%).
Claims (12)
1. produce the method for following formula (I) compound or its salt:
Wherein R is acyl group or silyl, and ring A and B can have 1-4 substituting group respectively, and this method comprises makes formula (II) compound or its salt:
Wherein the definition of R is the same, and ring A can have 1-4 substituting group on other position beyond the 2-position, and the reaction in the presence of the catalyzer beyond the Tripyrophosphoric acid of formula (III) compound or its salt:
Wherein Y is hydroxyl or halogen, and ring B can have 1-4 substituting group.
2. according to the process of claim 1 wherein that the ring A of compound (I) is at the 5-substd.
3. according to the process of claim 1 wherein that the ring A of compound (I) is at 4-position and 5-substd.
4. according to the process of claim 1 wherein that catalyzer is a friedel-crafts catalysts.
5. according to the method for claim 4, wherein friedel-crafts catalysts is a metal halide.
6. according to the method for claim 5, wherein metal halide is a tin halides.
7. according to the method for claim 4, wherein also use phosphorous oxychloride or phosphorus trichloride as catalyzer.
8. according to the process of claim 1 wherein that the substituting group on ring A and/or the B is respectively the hydroxyl that replaces, replace or unsubstituted alkyl, replace or unsubstituted acyl, perhaps halogen atom.
9. according to the process of claim 1 wherein that at least one substituting group on ring A or the B is C
1-6Alkoxyl group.
10. according to the process of claim 1 wherein that the substituting group on ring A and the B is respectively two C
1-6Alkoxyl group.
11. according to the process of claim 1 wherein that R is a formula :-CO-R
1Group, R wherein
1Be to replace or unsubstituted C
1-6Alkyl.
12. according to the process of claim 1 wherein that R is an ethanoyl.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29211896 | 1996-11-01 | ||
| JP292118/96 | 1996-11-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1181376A true CN1181376A (en) | 1998-05-13 |
Family
ID=17777785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 97120201 Pending CN1181376A (en) | 1996-11-01 | 1997-10-31 | Production of benzophenone derivatives |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0839801A3 (en) |
| CN (1) | CN1181376A (en) |
| CA (1) | CA2219620A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1113840C (en) * | 1999-11-26 | 2003-07-09 | 石彩云 | Synthesis method of alpha-hydroxycyclohexylbenzyl ketone |
| CN102329207A (en) * | 2011-10-18 | 2012-01-25 | 黄石理工学院 | Synthesis method of 2, 2'-dihydroxy-4, 4'-dimethoxybenzophenone |
| CN103224436A (en) * | 2013-05-03 | 2013-07-31 | 温州大学 | Preparation method of o-amino diaryl ketone compound |
| CN103265420A (en) * | 2013-05-03 | 2013-08-28 | 温州大学 | Preparation method of aromatic diketone compound |
| CN103274916A (en) * | 2013-04-28 | 2013-09-04 | 温州大学 | Alkyl and aryl ketone compound preparation method |
| US8731392B2 (en) | 2008-04-25 | 2014-05-20 | Osram Opto Semiconductors Gmbh | Illumination unit |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2789990B1 (en) * | 1999-02-22 | 2002-04-05 | Rhodia Chimie Sa | PROCESS FOR THE PREPARATION OF AMINOBENZOPHENONE DERIVATIVES |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2078538A (en) * | 1934-11-20 | 1937-04-27 | Gen Aniline Works Inc | 4,5-alkylsubstituted 2-aminodiarylketones and process of preparing them |
| JP2894804B2 (en) * | 1989-07-19 | 1999-05-24 | 武田薬品工業株式会社 | 2-Amino-5-methylbenzophenones and their production |
-
1997
- 1997-10-29 CA CA 2219620 patent/CA2219620A1/en not_active Abandoned
- 1997-10-30 EP EP97118871A patent/EP0839801A3/en not_active Withdrawn
- 1997-10-31 CN CN 97120201 patent/CN1181376A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1113840C (en) * | 1999-11-26 | 2003-07-09 | 石彩云 | Synthesis method of alpha-hydroxycyclohexylbenzyl ketone |
| US8731392B2 (en) | 2008-04-25 | 2014-05-20 | Osram Opto Semiconductors Gmbh | Illumination unit |
| CN102329207A (en) * | 2011-10-18 | 2012-01-25 | 黄石理工学院 | Synthesis method of 2, 2'-dihydroxy-4, 4'-dimethoxybenzophenone |
| CN103274916A (en) * | 2013-04-28 | 2013-09-04 | 温州大学 | Alkyl and aryl ketone compound preparation method |
| CN103224436A (en) * | 2013-05-03 | 2013-07-31 | 温州大学 | Preparation method of o-amino diaryl ketone compound |
| CN103265420A (en) * | 2013-05-03 | 2013-08-28 | 温州大学 | Preparation method of aromatic diketone compound |
| CN103265420B (en) * | 2013-05-03 | 2015-09-02 | 温州大学 | A kind of preparation method of aromatic diketone compound |
| CN103224436B (en) * | 2013-05-03 | 2015-09-02 | 温州大学 | The preparation method of the amino diaryl ketone compound of a kind of neighbour |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2219620A1 (en) | 1998-05-01 |
| EP0839801A2 (en) | 1998-05-06 |
| EP0839801A3 (en) | 1998-11-11 |
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